Current Advances in Genetic Dementia and Aging

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About this Research Topic

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Background

With the advancement of genetic technologies, more genetic risk factors of dementia have been identified. Approximately 25% of the population aged 55 years and older have a family history of dementia. The inheritance of dementia is complex. It can cause by a single-gene mutation. However, in most cases, it is related to multi-gene variants, which means genetic variations of little effects might combine to increase the risk of dementia. The lifetime risk of dementia for people with family history is about 20%, compared to 10% for the general population. These dementias mainly include early-onset Alzheimer’s disease (APP, PSEN1, and PSEN2 genes), frontotemporal dementia (MAPT, GRN, C9ORF72, and other genes), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (NOTCH3 gene), and other familial dementias.

Several large clinical trials have been conducted to investigate the disease characteristics of genetic dementia. For instance, the Anti-Amyloid Treatment in Asymptomatic Alzheimer disease (A4) Study aims to explore the association between elevated amyloid and demographic and lifestyle variables, apolipoprotein E (APOE), neuropsychological testing, and subjective and objective cognitive function. The Dominantly Inherited Alzheimer Network (DIAN) has reported some biomarkers of cognitive function through a longitudinal study. In 2015, multiple centers in the United States and Western Canada have launched the overlapping Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) studies to promote clinical trials of new therapies to prevent FTD.

Despite advancements in the field, many aspects of genetic dementia remain uncertain. The precise involvement of various genes in genetic dementia is still unclear. Also, we still need more studies to clarify the association between the clinical characteristics and different genetic biomarkers in genetic dementia. The diagnostic and prognostic applications of advanced functional magnetic resonance imaging and PET/CT in genetic dementia are still under investigation.

This Research Topic aims to address the key research questions of genetic dementia and aging, including 1. Studying how the various genes are involved in the pathogenesis of genetic dementia during aging; 2. Identifying clinical and radiological biomarkers associated with genetic dementia in the aging; 3. Improving clinical management and treatment of genetic dementia in aging. All these studies will offer potential novel therapeutic strategies for genetic dementia in aging.

Potential topics include, but are not limited to:
- Assessing the longitudinal changing pattern of CSF/serum biomarkers, cognitive function, and clinical courses in genetic dementia and aging
- Exploring the role of epigenetics, neuroimmune, and metabolism in the pathogenesis of genetic dementia and aging.
- Comparing the genetic and clinical differences between genetic dementia and other types of cognitive impairment and dementia in aging
- Identifying highly sensitive and specific biomarkers for the diagnosis and prognosis of genetic dementia in aging
- Exploring the dynamic changes of brain structure in genetic dementia in aging using functional magnetic resonance imaging (fMRI) and PET/CT and assessing its diagnostic value
- Evaluating the impact of risk factors, the outcome of drug treatment, and non-pharmacological intervention on the prevention and postponement of the onset of genetic dementia in aging

Keywords: Genetic Dementia, Aging, Alzheimer’s disease, Clinical Trails

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